This K23 Career Development Award application has been designed to launch the academic research career of the candidate, Dr. Jennifer Tremmel. Dr. Tremmel is a Cardiologist at Stanford, trained in both preventive and interventional cardiology, whose career goals are to become an independent clinical investigator and thought leader in the fields of women's cardiovascular health and sex differences in cardiovascular disease. Her career development plan centers on the research question of whether or not there is a sex difference in the pathophysiology of coronary artery disease. Specifically, she asks if women presenting with symptoms suggestive of angina, but demonstrating no angiographic evidence of obstructive coronary artery disease, are more likely than similarly presenting men to have coronary endothelial dysfunction, coronary microvascular disease, and diffuse deposition of coronary atherosclerotic plaque. Her specific aims are: 1. To compare the incidence and severity of coronary endothelial dysfunction between women and men using intracoronary acetylcholine (Ach) and quantitative coronary angiography (QCA). 2. To compare the incidence and severity of coronary microvascular disease between women and men using the coronary pressure wire to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). 3. To compare the epicardial artery atherosclerotic burden and distribution between women and men using intravascular ultrasound (IVUS). Her development plan is designed around this research, focusing on development in four key areas: 1) Sex- Based Medicine, 2) Advanced Statistical Analysis and Data Interpretation, 3) Vascular Biology, and 4) Non- invasive techniques for assessing endothelial function and coronary pathophysiology. This development will allow her to successfully conduct her research proposal and will prepare her for the next phase of her career as an independent investigator. Dr. Tremmel will be conducting her research in a premier academic environment under the supervision of outstanding mentors and collaborators. RELEVANCE (See instructions): This research has a direct relevance to public health. The burden of cardiovascular disease is great and there is a growing body of evidence describing differences between the sexes. Continued investigation into these sex differences will add to our knowledge regarding sex-based outcome disparities and should prompt a change in our current approach to diagnosis and treatment, particularly among women. (End of Abstract)